药学学报, 2020, 55(12): 2924-2933
引用本文:
安梦瑶, 葛鹏, 胡雷, 钟飞, 周博宇, 刘昌孝. 血液灌流清除慢性肾病代表性毒素频度和效果的研究[J]. 药学学报, 2020, 55(12): 2924-2933.
AN Meng-yao, GE Peng, HU Lei, ZHONG Fei, ZHOU Bo-yu, LIU Chang-xiao. Safety and effectiveness of hemoperfusion on the removal of uremic toxins in chronic kidney disease[J]. Acta Pharmaceutica Sinica, 2020, 55(12): 2924-2933.

血液灌流清除慢性肾病代表性毒素频度和效果的研究
安梦瑶1,2, 葛鹏2, 胡雷2, 钟飞2, 周博宇2, 刘昌孝1,2,3
1. 天津大学化工学院制药工程, 天津 300072;
2. 天津天诚新药评价有限公司, 天津 300301;
3. 天津药物研究院, 释药技术与药物代谢动力学国家重点实验室, 天津 300193
摘要:
通过使用特殊定制血液灌流器,评价在相同实验周期不同频次下血液灌流(hemoperfusion,HP)对慢性肾病(chronic kidney disease,CKD)比格犬治疗的安全性和有效性。动物实验方案由天津药物研究院新药评价有限公司伦理委员会审核并批准(IACUC批准号为2019071501)。CKD比格犬随机分为两组:低频率治疗组(7天/次,n=6)和高频率治疗组(3天/次,n=6),均进行两次HP治疗。评价比格犬血液学、血清生化、凝血功能、电解质、呼吸、心电图和血压等指标。高频率HP治疗可以明显减少毒素在CKD比格犬体内蓄积。血液学、凝血功能、电解质、肝功能、呼吸、心电图和血压等指标证明了使用特制血液灌流器进行HP治疗是一种安全的方法,且高频率治疗组对机体的各指标影响与低频率组比较无显著差异,所以,3天1次HP治疗在动物实验水平是安全的。实验证明,比临床推广方案(7天1次HP治疗)更高频率的3天1次治疗未造成机体实质性危害,未出现安全隐患,且更利于毒素清除,利于患者预后。
关键词:    慢性肾病      比格犬      尿毒素      血液灌流      血液净化     
Safety and effectiveness of hemoperfusion on the removal of uremic toxins in chronic kidney disease
AN Meng-yao1,2, GE Peng2, HU Lei2, ZHONG Fei2, ZHOU Bo-yu2, LIU Chang-xiao1,2,3
1. Department of Pharmaceutical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China;
2. Tianjin Tiancheng New Drug Evaluation Research Co., Ltd., Tianjin 300301, China;
3. State Key Laboratory of Drug Delivery Technology and Pharmacokinetics, Tianjin Institute of Pharmaceutical Research, Tianjin 300193, China
Abstract:
The goal of the present study was to determine the effectiveness and safety of hemoperfusion (HP) in beagle dogs with chronic kidney disease (CKD). The experimental protocol was approved by the Institutional Animal Care and Use Committee of Tianjin Institute of Pharmaceutical Research New Drug Evaluation Research (IACUC2019071501). Twelve CKD model beagles were randomly divided into two groups: a low-frequency treatment group (n=6) and a high-frequency treatment group (n=6). The dogs in the high- and low-frequency groups received HP treatment every 3 days and once per week, respectively, for two treatments, with each session lasting 2 h. The test results showed that high-frequency HP treatment significantly decreased the accumulation of toxins in the CKD beagles. Hematology, coagulation function, electrolytes and liver function indicated that the HP treatment was safe. The body index effects were consistent between the low- and high-frequency treatment groups. Therefore, HP treatment once every 3 days was safe at the animal level. Multiple HP treatments every 3 days were more conducive than weekly treatments to the removal of uremic toxins with better prognosis and had no associated safety hazards.
Key words:    chronic kidney disease    beagle dog    uremic toxin    hemoperfusion    blood purification   
收稿日期: 2020-09-24
DOI: 10.16438/j.0513-4870.2020-1533
基金项目: 国家科技重大新药创制项目(2015ZX09501004);天津市科技计划项目(16PTGCCX00090).
通讯作者: 刘昌孝,Tel:86-22-23006860,E-mail:liuchangxiao@163.com
Email: liuchangxiao@163.com
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